Vac14 Controls PtdIns(3,5) P 2 Synthesis and Fab1-Dependent Protein Trafficking to the Multivesicular Body

Ubiquitylation is a key regulator of protein trafficking, and much about the functions of ubiquitin ligases, which add ubiquitin to substrates in this regulation, has recently come to light. However, a clear understanding of ubiquitin-dependent protein localization cannot be achieved without knowledge of the role of deubiquitylating enzymes (DUBs). DUBs, by definition, function downstream in ubiquitin pathways and, as such, have the potential to be the final editors of protein ubiquitylation status, thus determining substrate fate. This paper assimilates the current evidence concerning the substrates and activities of DUBs that regulate protein trafficking.

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Faculty Opinions recommendation of Ent5p is required with Ent3p and Vps27p for ubiquitin-dependent protein sorting into the multivesicular body.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1019464.218577 ◽

2004 ◽

Author(s):

Robert Michell

Keyword(s):

Protein Sorting ◽

Multivesicular Body ◽

Dependent Protein

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UNC-108/Rab2 Regulates Postendocytic Trafficking inCaenorhabditis elegans

Molecular Biology of the Cell ◽

10.1091/mbc.e07-11-1120 ◽

2008 ◽

Vol 19 (7) ◽

pp. 2682-2695 ◽

Cited By ~ 40

Author(s):

Denise K. Chun ◽

Jason M. McEwen ◽

Michelle Burbea ◽

Joshua M. Kaplan

Keyword(s):

Protein Trafficking ◽

Fluorescent Protein ◽

Neuronal Cell ◽

Multivesicular Body ◽

Degradation Pathway ◽

Recycling Endosomes ◽

Alternative Pathways ◽

Ventral Cord ◽

Neuronal Cell Bodies ◽

Green Fluorescent

After endocytosis, membrane proteins are often sorted between two alternative pathways: a recycling pathway and a degradation pathway. Relatively little is known about how trafficking through these alternative pathways is differentially regulated. Here, we identify UNC-108/Rab2 as a regulator of postendocytic trafficking in both neurons and coelomocytes. Mutations in the Caenorhabditis elegans Rab2 gene unc-108, caused the green fluorescent protein (GFP)-tagged glutamate receptor GLR-1 (GLR-1::GFP) to accumulate in the ventral cord and in neuronal cell bodies. In neuronal cell bodies of unc-108/Rab2 mutants, GLR-1::GFP was found in tubulovesicular structures that colocalized with markers for early and recycling endosomes, including Syntaxin-13 and Rab8. GFP-tagged Syntaxin-13 also accumulated in the ventral cord of unc-108/Rab2 mutants. UNC-108/Rab2 was not required for ubiquitin-mediated sorting of GLR-1::GFP into the multivesicular body (MVB) degradation pathway. Mutations disrupting the MVB pathway and unc-108/Rab2 mutations had additive effects on GLR-1::GFP levels in the ventral cord. In coelomocytes, postendocytic trafficking of the marker Texas Red-bovine serum albumin was delayed. These results demonstrate that UNC-108/Rab2 regulates postendocytic trafficking, most likely at the level of early or recycling endosomes, and that UNC-108/Rab2 and the MVB pathway define alternative postendocytic trafficking mechanisms that operate in parallel. These results define a new function for Rab2 in protein trafficking.

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Loss of CHIP Expression Perturbs Glucose Homeostasis and Leads to Type II Diabetes through Defects in Microtubule Polymerization and Glucose Transporter Localization

10.1101/166389 ◽

2017 ◽

Cited By ~ 1

Author(s):

Holly McDonough ◽

Kaitlin C. Lenhart ◽

Sarah M. Ronnebaum ◽

Chunlian Zhang ◽

Jie An ◽

...

Keyword(s):

Glucose Homeostasis ◽

Protein Trafficking ◽

Type Ii Diabetes ◽

Glucose Transporter ◽

Protein A ◽

Whole Body ◽

Type Ii ◽

Interacting Protein ◽

Microtubule Polymerization ◽

Dependent Protein

ABSTRACTRecent evidence has implicated CHIP (carboxyl terminus of Hsc/Hsp70-interacting protein), a co-chaperone and ubiquitin ligase, in the functional support of several metabolism-related proteins, including AMPK and SirT6. In addition to previously reported aging and stress intolerance phenotypes, we find that CHIP -/- mice also demonstrate a Type II diabetes-like phenotype, including poor glucose tolerance, decreased sensitivity to insulin, and decreased insulin-stimulated glucose uptake in isolated skeletal muscle, characteristic of insulin resistance. In CHIP-deficient cells, glucose stimulation fails to induce translocation of Glut4 to the plasma membrane. This impairment in Glut4 translocation in CHIP-deficient cells is accompanied by decreased tubulin polymerization associated with decreased phosphorylation of stathmin, a microtubule-associated protein required for polymerization-dependent protein trafficking within the cell. Together, these data describe a novel role for CHIP in regulating microtubule polymerization that assists in glucose transporter translocation, promoting whole-body glucose homeostasis and sensitivity to insulin.

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Eeyarestatin 24 impairs SecYEG‐dependent protein trafficking and inhibits growth of clinically relevant pathogens

Molecular Microbiology ◽

10.1111/mmi.14589 ◽

2020 ◽

Author(s):

Maurice Steenhuis ◽

Gregory M. Koningstein ◽

Julia Oswald ◽

Tillman Pick ◽

Sarah O’Keefe ◽

...

Keyword(s):

Protein Trafficking ◽

Dependent Protein

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AtCAP2 is crucial for lytic vacuole biogenesis during germination by positively regulating vacuolar protein trafficking

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1717204115 ◽

2018 ◽

Vol 115 (7) ◽

pp. E1675-E1683 ◽

Cited By ~ 5

Author(s):

Yun Kwon ◽

Jinbo Shen ◽

Myoung Hui Lee ◽

Kyoung Rok Geem ◽

Liwen Jiang ◽

...

Keyword(s):

Plant Development ◽

Protein Trafficking ◽

Adaptor Protein ◽

Mature Stage ◽

Loss Of Function ◽

Calcium Dependent ◽

Dependent Protein ◽

Lytic Vacuole ◽

Vacuolar Protein ◽

Vacuole Biogenesis

Protein trafficking is a fundamental mechanism of subcellular organization and contributes to organellar biogenesis. AtCAP2 is an Arabidopsis homolog of the Mesembryanthemum crystallinum calcium-dependent protein kinase 1 adaptor protein 2 (McCAP2), a member of the syntaxin superfamily. Here, we show that AtCAP2 plays an important role in the conversion to the lytic vacuole (LV) during early plant development. The AtCAP2 loss-of-function mutant atcap2-1 displayed delays in protein storage vacuole (PSV) protein degradation, PSV fusion, LV acidification, and biosynthesis of several vacuolar proteins during germination. At the mature stage, atcap2-1 plants accumulated vacuolar proteins in the prevacuolar compartment (PVC) instead of the LV. In wild-type plants, AtCAP2 localizes to the PVC as a peripheral membrane protein and in the PVC compartment recruits glyceraldehyde-3-phosphate dehydrogenase C2 (GAPC2) to the PVC. We propose that AtCAP2 contributes to LV biogenesis during early plant development by supporting the trafficking of specific proteins involved in the PSV-to-LV transition and LV acidification during early stages of plant development.

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